A variable clinical profile
The clinical profile of Lassa fever varies from asymptomatic infection, which occurs in 80% of cases, to acute hemorrhagic fever. The onset of the disease occurs 6 to 21 days after infection, with non-specific clinical signs: fever, vomiting, nausea, abdominal pain, headache, muscle or joint pain or weakness. In severe cases, the symptoms then get worse, with the emergence of edema, hemorrhagic signs, pericardial and pleural effusion, and more rarely encephalitis.
Death occurs as a result of hypotensive and hypovolemic shock and kidney and liver failure.
Lassa fever is extremely severe for pregnant women, resulting in frequent maternal death and systematic fetal loss.
Possible sequelae in survivors
In patients who survive Lassa fever infection, fever disappears around 10 days after the onset of symptoms, but extreme fatigue, malaise and dizziness can continue for several weeks. A third of these patients develop severe sequelae: temporary or permanent hearing loss in one or both ears, and myocarditis.
An endemic virus in West Africa
Lassa virus was named after the town in Nigeria where it was first isolated in 1969 in a nurse who fell ill after treating patients and who died from the disease after contaminating two other healthcare workers.
Lassa fever is endemic in Nigeria, Guinea, Liberia and Sierra Leone, where outbreaks occur regularly. The incidence of the disease has risen in recent years as a result of an influx of political refugees to the affected areas. Although no cases have been described in Côte d'Ivoire or Ghana, these countries could potentially also be affected by the virus. Finally, Lassa fever is the most frequently imported hemorrhagic fever to northern countries, with more than 20 cases recorded since 1969.
A small domestic rodent is the viral reservoir
The main reservoir of the Lassa virus is Mastomys natalensis, a small peridomestic rodent. The virus spreads to humans when they come into contact with the animal's excreta (urine or feces). Many of these rodents live near or inside housing, and their rate of infection can be as high as 80%. Contacts between humans and the infected reservoir are therefore very frequent in villages, and up to 50% of individuals living in endemic areas can be infected. The virus can also spread between humans, mainly in hospital environments, if mucous membranes or broken skin are exposed to a patient's biological fluids.
Treatment and vaccine
An antiviral drug is available but unsuitable for use in the field
There is currently only one molecule that has proven to be effective in treating Lassa virus: ribavirin, a broad spectrum antiviral active against RNA viruses and particularly used to treat hepatitis C. This treatment does not represent a satisfactory solution to the problem of Lassa fever in endemic countries, however, since ribavirin is only effective if administered very early after infection. But the early clinical signs of the illness are similar to those observed for other diseases such as malaria and dysentery, which are widespread in these regions. Lassa virus is therefore often only considered as a possible diagnosis several days after the onset of symptoms, and in the rare cases where ribavirin is available, it is usually administered too late to be effective.
Promising vaccine candidates under investigation
Research is currently under way to develop a Lassa fever vaccine. Some vaccine candidates found to be effective in primates are under investigation. Most of them were developed from attenuated viral vectors expressing surface glycoproteins and/or the Lassa virus nucleoprotein. The protection afforded by these vaccines in monkeys seems to be dependent on the induction of cytotoxic lymphocyte responses. Since the immune mechanisms elicited in humans who survive Lassa fever are probably similar, these vaccine strategies are promising.
At the Institut Pasteur
Lassa virus can only be handled in a high-security BSL-4 laboratory. The only laboratory of this kind currently in France is the Jean-Mérieux BSL-4 laboratory in the Gerland district of Lyon. Since the 2000s, the Institut Pasteur has had a resident team in Lyon with access to this laboratory, the Biology of Viral Emerging Infections Unit (led by Sylvain Baize), which works on the Lassa virus and also hosts the National Reference Center for Viral Hemorrhagic Fevers.
The WHO Collaborating Center for Reference and Research on Arboviruses and Viral Hemorrhagic Fevers, led by Sylvain Baize, also focuses on arenaviruses and other viral hemorrhagic fevers transmitted by rodents, arthropods or bats. The aim of the scientists' research is to improve understanding of the interactions between the virus and host target cells, either using animal models or in vitro in humans. Another area of investigation is the mechanisms employed by the virus to cross the species barrier between animals and humans, especially the question of why the virus is not pathogenic for the animal reservoir but becomes pathogenic in humans. A further topic of study aims to shed light on the cellular immune mechanisms that either enable control of the infection or lead to death in humans. This research should improve understanding of the pathophysiology of the hemorrhagic fever and could serve as a basis for the development of a therapy or a vaccine.
The Institut Pasteur teams working on the topic
Biology of Viral Emerging Infections Unit led by Sylvain Baize
Antiviral Strategies Unit led by Noël Tordo
Laboratory for Urgent Response to Biological Threats led by Jean-Claude Manuguerra
Surveillance and public health : WHO Collaborating Center for Arboviruses and Viral Hemorrhagic Fevers
led by Sylvain Baize